Macrocyclic polyethers or "crown ethers" have been known for a number of years, C. J. Pedersen of DuPont being credited with the invention thereof (See U.S. Pat. No. 3,687,978; and Pedersen, J. Amer. Chem. Soc., 89, 7017-7036 (1967). These materials have particular utility in their remarkable ability to complex with numerous elements (See U.S. Pat. No. 3,686,225 to Pedersen). A typical crown ether has the following structure: ##STR1##
Since the development of the original crown ethers, considerable work has been done on substituted crown ethers. For example, the patent to Kauer, U.S. Pat. No. 3,997,565, discloses certain acyl crown ether oximes, oxime ethers and oxime esters useful as complexing agents, dispersing agents for carbon black, and antiviral agents. In U.S. Pat. No. 4,024,158 Kauer discloses various aroyl crown ethers having a wide variety of substituent groups directly attached to a benzo group. U.S. Pat. No. 4,001,279 to Cram shows another modification of crown ethers to provide chiral, hinged and functionalized host multiheteromacrocycles containing oxygen, nitrogen and/or sulfur and possessing holes sized to afford selective complexation of specific guest substances, the provision of ortho positioned side chain substituents or "arms" bearing terminal functional groups which act as counterions or additional complexing sites, and the provision of remote position side chain substituents used to control solubility and volatility properties or to bond the multiheteromacrocycles to solid supports.
Another class of crown ethers is described as "cryptates" which are especially useful in forming stable complexes as described in U.S. Pat. No. 3,966,766 to Lehn, and Tetrahedron Lett., 1979, (36), 3485-3486 (Eng.).
The foregoing references are illustrative of some of the modifications of that important new class of materials. Generally speaking, the simpler crown ethers are made by reacting 2 molecules of a dihydric phenol, e.g., catechol, with 2 molecules of an alkyl dihalide or alkyl ether dihalide in the presence of 4 molecules of alkali metal hydroxide, e.g., NaOH (See Pedersen U.S. Pat. No. 3,687,978). The other illustrative references referred to above disclose similar reactions.
The present invention provides a novel method of making a modified crown ether of the various types described in the art having functionality which, instead of being attached directly or indirectly to a hydrocarbyl ring (for example, a benzo group), is attached directly to a carbon atom in the polyether portion of the molecule. All the products hereof may be used as complexing agents in the same way and for the same purposes as chelating agents.
The process for making these novel crown ethers which have a functional group "handle" on the polyether ring is also believed to be novel. It has been found not to be practical to introduce functional groups onto the polyether rings of existing crown ethers. Therefore, such functional groups must be incorporated prior to or concomitant with ring closure. A reported example of the synthesis of crown ethers bearing functional group "handles" on the polyether rings (a), (b), and (c), is shown below. While it is possible to prepare the "functionalized" ##STR2## crown ethers (a), (b), and (c) by these reaction series, the process, albeit novel, is costly and does not lend itself to industrial application.
What has now been found is an industrially practical synthesis for functionalized crown ethers wherein the polyether ring is provided with at least one functional group.
The closest prior art of which I am aware is an article entitled "A Modified Synthesis of Dibenzo-18-Crown-6-Polyether and Related Macrocycles", by Ashby et al., "Synthetic Communications", 4(2), 113-117 (1974). According to this article an amidic diphenol (d) was reacted with sodium hydroxide and 1-chloro-2,3-epoxypropane under conditions of high dilution to produce a low yield (12%) of cyclized product (e). Examination of three ##STR3## dimensional models suggests that the amide linkages may play an essential role in the ring closure reaction. First, hydrogen-bonding interactions may produce conformations of the diphenoxide (f) in which the two negatively charged oxygens are brought into proximity, thus favoring ring closure. Alternatively, one of the ##STR4## amide groups may facilitate ring closure by producing favorable interactions within a reaction intermediate, for example (g). Therefore, it seems ##STR5## reasonable to expect that the amide groups were important to the success of the ring closure reactions (d).fwdarw.(e).
In the case of the present invention, the ring heteroatoms are oxygen and no amide linkages are present. Surprisingly, it has been found that effective ring closure occurs with the diphenol ethers used in the present invention and that the yields of ring closure products are several times higher than that reported by Ashby et al., for the cyclization of the amidic diphenol (d).
According to the prior art the yield was 12%. A three dimensional model of the starting material prior to ring closure indicates that the presence of N tends to favor ring closure. In the case of the present invention where the hetero atoms are oxygen, ring closure is not favored. Surprisingly, however, not only has effective ring closure been found to occur with the diphenol ethers used in the present invention, but the yield is several times that obtained where nitrogen is present in the ring.